Basement membrane laminin-5 is deposited in colorectal adenomas and carcinomas and serves as a ligand for α3β1 integrin
Abstract:Interplay between laminin-5 ( Ln-5) and its integrin ( Int) receptors α2β1, α3β1 and α6β4 has been implicated in the progression and invasion of carcinomas. In this study we found abundant immunoreactivity for chains of Ln-5 (α3-β3-γ2) and Ln-10 (α5-β1-γ1), as well as for type VII collagen, in basement membranes ( BM) of colorectal adenomas. In carcinomas of all differentiation grades, Lns were seen in tumor BMs, whereas type VII collagen was almost absent. Ln-5 appeared to accumulate along the invading edges of carcinomas, while Ln-10 was mostly absent. Immunoreactivity for Ln α1 chain, a component of Lns-1 and -3, was not seen in adenomas or carcinomas. Immunoreactivity for α2, α6, β1 and β4 Ints was found in all tumors and that for α3 Int in all adenomas and most of the carcinomas, often in colocalization with Ln-5. Immunoblotting of carcinoma tissues showed that the γ2 chain of Ln-5 was present as typical Mr 105000 and 155000 isoforms. Immunoprecipitation experiments showed production of Ln-5 by cultured colon carcinoma cells. In quantitative cell adhesion experiments, function-blocking MAbs to α3 and β1 Int subunits, but not those to Int α2 or α6 subunits, significantly inhibited the adhesion of cells to Ln-5. Our results suggest that BM composition in colorectal adenomas reflects the properties of surface epithelial BM of colorectal mucosa. In invading carcinomas, trimeric Ln-5, produced by carcinoma cells, is a major BM component and the cells use the α3β1 Int complex for adhesion to Ln-5.
Document Type: Original Article
Affiliations: 1: Department of Anatomy, Institute of Biomedicine, University of Helsinki; 2: Second Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland 3: Craniofacial Devel. Biol. Regen. Branch, Bethesda; 4: Cutaneous Biology Research Center, Harvard Medical School, Massachusetts General Hospital, Charlestown, USA 5: Department of Pathology, University of Helsinki, Finland
Publication date: March 1, 2000